sign in sign up
<<
Home , Reactive hypoglycemia

Khanimov I, et al., J Food Sci Nutr 2019: S1001 DOI: 10.24966/FSN-1076/S1001 HSOA Journal of Food Science and Nutrition Review Article Special Issue

Malnutrition and Classification of hypoglycemia According to the report of the workgroup of the American Dia- Risk among Patients with Dia- betes Association and The Endocrine Society, hypoglycemia can be betes Mellitus classified as follows [6]. Severe hypoglycemia: Severe hypoglycemia is an event requiring Khanimov I1, Wainstein J1,2, Shimonov M1,3 and Leibovitz E4* assistance of another person to actively administer , 1Sackler School of , Tel Aviv University, Tel Aviv, Israel , or take other corrective actions. Plasma concentra- tions may not be available during an event, but neurological recovery 2Diabetes Unit, Wolfson Medical Center, Holon, Israel following the return of plasma glucose to normal is considered suf- 3Department of “A”, E. Wolfson Medical Center, Holon, Israel ficient evidence that the event was induced by a low plasma glucose concentration. 4Department of “A”, Yoseftal Hospital, Eilat, Israel Documented symptomatic hypoglycemia: Documented symptom- atic hypoglycemia is an event during which typical symptoms of hy- Abstract poglycemia are accompanied by a measured plasma glucose concen- tration ≤70mg/dL (≤3.9mmol/L). Hypoglycemia is associated with increased risk of morbidity and mortality, and is detrimental to patients regardless of Diabetes Mel- Asymptomatic hypoglycemia: Asymptomatic hypoglycemia is an litus (DM) status. Among patients with DM, hypoglycemia is consid- event not accompanied by typical symptoms of hypoglycemia but with ered a result of overtreatment of anti-diabetic agents (iatrogenic hy- a measured plasma glucose concentration ≤70mg/dL (≤3.9mmol/L). poglycemia). Among patients without DM, this condition is attributed to disease severity. Recently, high malnutrition risks, as well as other Probable symptomatic hypoglycemia: Probable symptomatic hypo- markers of malnutrition, were indicative of increased risk of hypogly- glycemia is an event during which symptoms typical of hypoglyce- cemia among hospitalized patients. In this review we focus on the mia are not accompanied by a plasma glucose determination but that relationship between hypoglycemia and malnutrition among patients was presumably caused by a plasma glucose concentration ≤70mg/ with and without DM. dL (≤3.9mmol/L). Keywords: Albumin; Diabetes mellitus; Hypoglycemia; Malnutrition; Nutrition Pseudo-hypoglycemia*: Pseudo-hypoglycemia is an event during which the person with diabetes reports any of the typical symptoms of Introduction hypoglycemia with a measured plasma glucose concentration >70mg/ dL (>3.9mmol/L) but approaching that level. Hypoglycemia can be defined as serum glucose level equal or un- *According to the previous report of the American Diabetes Asso- der 70mg/dL (≤3.9mmol/L) [1,2]. Among patients with diabetes mel- ciation workgroup on hypoglycemia from 2004, this state was defined litus, and in accordance with the International Hypoglycemia Study as “Relative hypoglycemia” [7]. Group guidelines, serum glucose under 54mg/dL (≤3.0mmol/L), is sufficiently low to indicate serious, clinically important hypoglyce- Risk factors and prognosis associated with hypoglycemia mia and thus should be routinely reported in clinical trials dealing with glucose-lowering agents [3]. For decades, it was assumed that Risk factors for hypoglycemia among hospitalized patients include serum glucose level is mostly regulated by two hormones- and DM, older age, disease severity, renal insufficiency, septic shock, me- glucagon. Nowadays, it is well known that glucose is chanical ventilation, tight glycemic control and increasing number of regulated by various glucoregulatory hormones which effect multiple anti diabetic agents [8,9]. Iatrogenic hypoglycemia is associated with target tissues, such as muscle, brain, liver, and adipocyte [4,5]. administration of insulin and insulin-secretagogues (sulfonylureas and meglitinides) [10]. *Corresponding author: Eyal Leibovitz, Department of Internal Medicine “A”, Yo- seftal Hospital, Eilat, Israel, Tel: +972 35028624; E-mail: [email protected] Documented hypoglycemia is associated with poor short and long Citation: Khanimov I, Wainstein J, Shimonov M, Leibovitz E (2019) Malnutrition term prognosis among patients admitted to internal medicine depart- and Hypoglycemia Risk among Patients with Diabetes Mellitus. J Food Sci Nut: ments regardless of Diabetes Mellitus (DM) status [11]. Among pa- S1001. tients with DM, hypoglycemia was repeatedly shown to be associated Received: March 11, 2019; Accepted: March 29, 2019; Published: April 08, with an increased length of hospital stay and decreased short and long 2019 term survival [9,11-13]. Moreover, hypoglycemia was found to be Copyright: © 2019 Khanimov I, et al. This is an open-access article distributed associated with an increased risk for dementia among older adults under the terms of the Creative Commons Attribution License, which permits un- with DM [14-16]. Association between morbidity and hypoglycemia restricted use, distribution, and reproduction in any medium, provided the original among patients without DM was documented as well [17-19]. While author and source are credited. the prevalence of hypoglycemia is higher among DM patients, the Citation: Khanimov I, Wainstein J, Shimonov M, Leibovitz E (2019) Malnutrition and Hypoglycemia Risk among Patients with Diabetes Mellitus. J Food Sci Nut: S1001.

• Page 2 of 5 •

prognosis of patients with hypoglycemia is worse among patients There are several surrogate markers for malnutrition that can be without DM [20]. This raises the possibility that the etiology of hypo- measured in the blood stream, serum albumin being the most fre- glycemia, rather than hypoglycemia per-se, is responsible for the poor quently used. Albumin level was shown to be influenced by nutrition- outcome observed. al status [40], however, there is still a controversy whether albumin level is a marker of nutrition status [41], because it plays a major role Spontaneous hypoglycemia in various medical conditions [42]. Interestingly, serum albumin is As described previously, hypoglycemia can also occur among as accurate a predictor of outcome as the APACHE II Score among hospitalized patients without DM. Unexpected severe (below 55mg/ Intensive Care Unit (ICU) patients [43]. Low albumin level is associ- dL, 3mmol/L) hypoglycemia in non-diabetic patients outside the in- ated with increased morbidity and mortality in many patient popula- tensive care unit was 36 per 10,000 admissions (95% CI 24-64), and tions [44,45]. more than 90% of the patients were admitted as emergency cases [21]. Other marker suggested as an indicator of malnutrition is serum Rate of hypoglycemia was higher among patients aged 65 and over. prealbumin (i.e transthyretin). The major source of this is in Hypoglycemia was more prevalent among patients with sepsis, kid- the liver [46] and it has a half-life of two days [47]. Moreover, serum ney disease, alcohol dependence, pneumonia, liver disease, cancer, level of prealbumin is not altered by hydration status [48]. A reverse and self-harm with hypoglycemic agents. Spontaneous hypoglycemia correlation was found between prealbumin level and mortality among may also occur among patients with DM, as was found among pa- hospitalized elderly patients with a decreased nutrient intake [49] and tients suffering from infection, with or without sepsis [22]. Postpran- patients treated with hemodialysis and peritoneal dialysis [50]. On dial (reactive) hypoglycemia may also be the cause of spontaneous the other hand, among critically ill patients with inflammation, se- hypoglycemia among patients with DM [23,24]. rum prealbumin level was not a sensitive marker for evaluating the Hypoglycemia and malnutrition adequacy of nutrition support. It was found that only change in CRP level was able to significantly predict changes in level of prealbumin, Malnutrition is defined as an imbalance between consumption and indicating that increase in prealbumin was as a result of improvement expenditure of either energy, protein or any other nutrient that damag- in inflammation, rather than nutrient intake [51]. es body function [25]. Additional markers of nutritional status include serum cholester- Several suggestions for classification of malnutrition were sug- ol. It was shown that among patients with DM, both total and LDL gested over the years, mostly in infants and children in developing cholesterol levels were lower in undernourished patients compared countries. In 1955, Gomez et al. [26], suggested a classification of to well-nourished [52]. This was true regardless of treatment with in- malnutrition in infancy and childhood based on child’s weight com- sulin. In a recently published systematic review and meta-analysis pared to that of a child in the 50th percentile of the same age. A later regarding the association between blood biomarkers and risk of mal- classification by Waterlow et al. [27], was based on z- Scores (SD) nutrition in older adults, it was found that serum albumin, prealbumin which took into account both weight and height of the child. The and total cholesterol are useful biochemical indicators of malnutri- World Health Organization (WHO) classification is based on Water- tion, even with the presence of chronic inflammation [53]. Recently low’s system with some modifications [28]. we showed that serum albumin and cholesterol levels measured at hospital admission, predict hypoglycemia in patients admitted to gen- Two major clinical syndromes of malnutrition include kwashior- eral internal medicine units, regardless of DM status [54]. kor (almost normal weight for age, marked generalized edema) and marasmus (depletion of subcutaneous fat stores, muscle wasting, and The mechanism responsible for hypoglycemia among malnour- absence of edema), though a mixed variant is also frequent [28]. ished patients is still unknown. A possible explanation might be a de- pletion of hepatic storage. Evidence to support the associa- Several types of malnutrition were described with different patho- tion of glycogen storage with hypoglycemia can be found in patients geneses [29]. For example, malnutrition can be induced by reduced that suffer from Glycogen Storage Disorders (GSDs). These disorders food intake due to diminished appetite, or as a result of impaired nu- are inborn errors of metabolism with abnormal storage or utilization trient absorption [30]. Other causes include older age, socio-econom- of glycogen, with a cardinal presenting feature of hypoglycemia [55]. ic status and comorbidities [31]. In 2015, about 795 million people In spite of the different pathophysiology of both conditions, they may were undernourished worldwide [32]. Prevalence of malnutrition is have the same clinical outcome, i.e., hypoglycemia. Other factors high among inpatients as well. In a study including 504 newly hospi- that may increase the likelihood of glycogen depletion include a shift talized adult patients, 159 of them (31.5%) were identified as being towards anaerobic metabolism. Further research is warranted to de- at high risk for malnutrition according to the Nutrition Risk Score termine the pathophysiology of hypoglycemia among malnourished (NRS) 2002 [33,34]. Other studies showed that as many as 50% of all patients. patients admitted to hospitals in western countries were malnourished or had an increased risk of malnutrition [35,36]. Conclusion and Recommendations In the developing world, it has been demonstrated that patients In conclusion, hypoglycemia is associated with poor short and with severe malnutrition (and hypoglycemia) may have Malnutri- long-term prognosis and increased morbidity and mortality. Hypo- tion-Related Diabetes Mellitus (MRDM), a rare type of diabetes asso- glycemia is more common among patients with DM, probably as a ciated with long term malnutrition [37,38]. Additionally, we showed result of anti-diabetic agents. However, it can occur among patients recently that one of the risk factors for hypoglycemia among patients without DM as well. After diagnosis of hypoglycemia is established, with and without DM was high risk for malnutrition as measured by a thorough evaluation of patient’s nutritional status is recommend- the NRS2002 [39]. ed because of high risk for malnutrition. This is true regardless of

Volume 5 • S1001 J Food Sci Nutr ISSN: 2470-1076, Open Access Journal DOI: 10.24966/FSN-1076/S1001

Citation: Khanimov I, Wainstein J, Shimonov M, Leibovitz E (2019) Malnutrition and Hypoglycemia Risk among Patients with Diabetes Mellitus. J Food Sci Nut: S1001.

• Page 3 of 5 •

DM status. We recommend that nutritional assessment includes both 16. Yaffe K, Falvey CM, Hamilton N, Harris TB, Simonsick EM, et al. (2013) laboratory tests as well as a referral to nutrition nurse, dietitian or Association between hypoglycemia and dementia in a biracial cohort of expert clinician for further evaluation, including nutrition risk screen- older adults with diabetes mellitus. JAMA Intern Med 173: 1300-1306. ing questionnaire and other nutritional and metabolic variables. A de- 17. Fischer KF, Lees JA, Newman JH (1986) Hypoglycemia in hospitalized tailed care plan should be established following careful monitoring patients. Causes and outcomes. N Engl J Med 315: 1245-1250. of outcomes. 18. Mannucci E, Monami M, Mannucci M, Chiasserini V, Nicoletti P, et al. (2006) Incidence and prognostic significance of hypoglycemia in hospital- Conflict of Interest ized non-diabetic elderly patients. Aging Clin Exp Res 18: 446-451. All the authors declare no conflict of interest. 19. Shilo S, Berezovsky S, Friedlander Y, Sonnenblick M (1998) Hypoglyce- mia in hospitalized nondiabetic older patients. J Am Geriatr Soc 46: 978- References 982.

1. Seaquist ER, Anderson J, Childs B, Cryer P, Dagogo-Jack S, et al. (2013) 20. Leibovitz E, Khanimov I, Wainstein J, Boaz M (2019) Documented hypo- Hypoglycemia and diabetes: A report of a workgroup of the American Di- glycemia is associated with poor short and long term prognosis among pa- abetes Association and The Endocrine Society. J Clin Endocrinol Metab tients admitted to general internal medicine departments. Diabetes Metab 98: 1845-1859. Syndr Clin Res Rev 13: 222-226. 2. Cryer PE (2009) Preventing hypoglycaemia: What is the appropriate glu- 21. Nirantharakumar K, Marshall T, Hodson J, Narendran P, Deeks J, et al. cose alert value? Diabetologia 52: 35-37. (2012) Hypoglycemia in non-diabetic in-patients: Clinical or criminal? PLoS One 7: 40384. 3. International Hypoglycaemia Study Group (2017) Glucose concentrations of less than 3.0mmol/L (54mg/dL) should be reported in clinical trials: A 22. Toda G, Fujishiro M, Yamada T, Shojima N, Sakoda H, et al. (2014) Lung joint position statement of the American Diabetes Association and the Eu- abscess without sepsis in a patient with diabetes with refractory episodes ropean Association for the study of diabetes. Diabetes Care 40: 155-157. of spontaneous hypoglycemia: A case report and review of the literature. J Med Case Rep 8: 51. 4. Wasserman DH (2009) Four grams of glucose. Am J Physiol Endocrinol Metab 296: 11-21. 23. Nydick M, Samols E, Kuzuya T, Williams RH (1964) A difficult diagnos- tic problem in spontaneous hypoglycemia. Reactive hypoglycemia in mild 5. Aronoff SL, Berkowitz K, Shreiner B, Want L (2004) Glucose metabolism diabetes mellitus. Ann intern med 61: 1122-1127. and regulation: Beyond insulin and glucagon. Diabetes Spectr 17: 183- 190. 24. Conn JW, Fajans SS, Seltzer HS (1956) Spontaneous hypoglycemia as an early manifestation of diabetes mellitus. Diabetes 5: 437-442. 6. Seaquist ER, Anderson J, Childs B, Cryer P, Dagogo-Jack S, et al. (2013) Hypoglycemia and diabetes: A report of a workgroup of the American Di- 25. Camilo ME (2003) Disease-related malnutrition: An evidence-based ap- abetes Association and The Endocrine Society. Diabetes Care 36: 1384- proach to treatment. Clinical Nutrition 22: 585. 1395. 26. Gomez F, Galvan RR, Cravioto J, Frenk S (1955) Malnutrition in infancy 7. Workgroup on Hypoglycemia, American Diabetes Association (2005) De- and childhood, with special reference to kwashiorkor. Adv Pediatr 7: 131- fining and reporting hypoglycemia in diabetes: A report from the Amer- 169. ican Diabetes Association Workgroup on Hypoglycemia. Diabetes Care 27. Waterlow JC (1972) Classification and definition of protein-calorie malnu- 28: 1245-1249. trition. Br Med J 3: 566-569. 8. Krinsley JS, Grover A (2007) Severe hypoglycemia in critically ill pa- 28. Grover Z, Ee LC (2009) Protein energy malnutrition. Pediatr Clin North tients: Risk factors and outcomes. Crit Care Med 35: 2262-2267. Am 56: 1055-1068. 9. Boucai L, Southern WN, Zonszein J (2011) Hypoglycemia-associated 29. Jensen GL, Bistrian B, Roubenoff R, Heimburger DC (2009) Malnutrition mortality is not drug-associated but linked to comorbidities. Am J Med syndromes: A conundrum vs continuum. JPEN J Parenter Enteral Nutr 33: 124: 1028-1035. 710-716. 10. Bonaventura A, Montecucco F, Dallegri F (2015) Update on strategies lim- 30. Campbell IT (1999) Limitations of nutrient intake. The effect of stressors: iting iatrogenic hypoglycemia. Endocr Connect 4: 37-45. Trauma, sepsis and multiple organ failure. Eur J Clin Nutr 1: 143-147. 11. Turchin A, Matheny ME, Shubina M, Scanlon JV, Greenwood B, et al. 31. Saunders J, Smith T (2010) Malnutrition: Causes and consequences. Clin (2009) Hypoglycemia and clinical outcomes in patients with diabetes hos- Med (Lond) 10: 624-627. pitalized in the general ward. Diabetes Care 32: 1153-1157. 32. McGuire S (2015) FAO, IFAD, and WFP. The State of Food Insecurity in 12. Zapatero A, Gómez-Huelgas R, González N, Canora J, Asenjo A, et al. the World 2015: Meeting the 2015 International Hunger Targets: Taking (2014) Frequency of hypoglycemia and its impact on length of stay, mor- Stock of Uneven Progress. Rome: FAO, 2015. Adv Nutr 6: 623-624. tality, and short-term readmission in patients with diabetes hospitalized in internal medicine wards. Endocr Pract 20: 870-875. 33. Rasmussen HH, Holst M, Kondrup J (2010) Measuring nutritional risk in hospitals. Clin Epidemiol 2: 209-216. 13. Brodovicz KG, Mehta V, Zhang Q, Zhao C, Davies MJ, et al. (2013) Asso- ciation between hypoglycemia and inpatient mortality and length of hos- 34. Giryes S, Leibovitz E, Matas Z, Fridman S, Gavish D, et al. (2012) MEa- pital stay in hospitalized, insulin-treated patients. Curr Med Res Opin 29: suring Nutrition risk in hospitalized patients: MENU, a hospital-based 101-107. prevalence survey. Isr Med Assoc J 14: 405-409.

14. Whitmer RA, Karter AJ, Yaffe K, Quesenberry CP, Selby JV (2009) Hy- 35. Edington J, Boorman J, Durrant ER, Perkins A, Giffin CV, et al. (2000) poglycemic episodes and risk of dementia in older patients with type 2 Prevalence of malnutrition on admission to four hospitals in England. The diabetes mellitus. JAMA 301: 1565-1572. Malnutrition Prevalence Group. Clin Nutr 19: 191-195. 15. Chaytor NS, Barbosa-Leiker C, Ryan CM, Germine LT, Hirsch IB, et al. 36. Correia MI, Campos AC, ELAN Cooperative Study (2003) Prevalence of (2019) Clinically significant cognitive impairment in older adults with hospital malnutrition in Latin America: The multicenter ELAN study. Nu- type 1 diabetes. J Diabetes Complications 33: 91-97. trition 19: 823-825.

Volume 5 • S1001 J Food Sci Nutr ISSN: 2470-1076, Open Access Journal DOI: 10.24966/FSN-1076/S1001

Citation: Khanimov I, Wainstein J, Shimonov M, Leibovitz E (2019) Malnutrition and Hypoglycemia Risk among Patients with Diabetes Mellitus. J Food Sci Nut: S1001.

• Page 4 of 5 •

37. Taksande A, Taksande B, Kumar A, Vilhekar KY, Taksande AM (2008) 47. Beck FK, Rosenthal TC (2002) Prealbumin: A marker for nutritional eval- Malnutrition-related diabetes mellitus symposium on diabetes. J MGIMS uation. Am Fam 65: 1575-1578. 13: 19-24. 48. Mears E (1996) Outcomes of continuous process improvement of a nutri- 38. Chattopadhyay PS, Gupta SK, Chattopadhyay R, Kundu PK, Chakraborti tional care program incorporating serum prealbumin measurements. Nu- R (1995) Malnutrition-Related Diabetes Mellitus (MRDM), not diabe- trition 12: 479-484. tes-related malnutrition. A report on genuine MRDM. Diabetes Care 18: 276-277. 49. Sullivan DH, Sun S, Walls RC (1999) Protein-energy undernutrition among elderly hospitalized patients: A prospective study. JAMA 281: 2013-2019. 39. Leibovitz E, Adler H, Giryes S, Ditch M, Burg NF, et al. (2018) Mal- nutrition risk is associated with hypoglycemia among general population 50. Sreedhara R, Avram MM, Blanco M, Batish R, Avram MM, et al. (1996) admitted to internal medicine units. Results from the MENU study. Eur J Prealbumin is the best nutritional predictor of survival in hemodialysis and Clin Nutr 72: 888-893. peritoneal dialysis. Am J Kidney Dis 28: 937-942. 40. Rothschild MA, Oratz M, Schreiber SS (1973) Progress in gastroenterolo- 51. Davis CJ, Sowa D, Keim KS, Kinnare K, Peterson S (2012) The use of pre- gy albumin metabolism. 64: 324-337. albumin and C-reactive protein for monitoring nutrition support in adult patients receiving enteral nutrition in an urban medical center. J Parenter 41. Lee JL, Oh ES, Lee RW, Finucane TE (2015) Serum albumin and prealbu- Enter Nutr 36: 197-204. min in calorically restricted, nondiseased individuals: A systematic review. Am J Med 128: 1023. 52. Das S, Tripathy BB, Samal KC, Panda NC (1984) Plasma lipids and li- poprotein cholesterol in undernourished diabetic subjects and adults with 42. Fanali G, di Masi A, Trezza V, Marino M, Fasano M, et al. (2012) Human protein energy malnutrition. Diabetes Care 7: 579-586. serum albumin: From bench to bedside. Mol Aspects Med 33: 209-290. 53. Zhang Z, Pereira S, Luo M, Matheson E (2017) Evaluation of blood bio- 43. McCluskey A, Thomas AN, Bowles BJ, Kishen R (1996) The prognostic markers associated with risk of malnutrition in older adults: A systematic value of serial measurements of serum albumin concentration in patients review and meta-analysis. Nutrients 9: 829. admitted to an intensive care unit. Anaesthesia 51: 724-727. 54. Leibovitz E, Wainstein J, Boaz M (2018) Association of albumin and cho- 44. Numeroso F, Barilli AL, Delsignore R (2008) Prevalence and significance lesterol levels with incidence of hypoglycaemia in people admitted to gen- of hypoalbuminemia in an internal medicine department. Eur J Intern Med eral internal medicine units. Diabet Med 35: 1735-1741. 19: 587-591. 55. Burda P, Hochuli M (2015) Hepatic glycogen storage disorders: What have 45. Vincent JL, Dubois MJ, Navickis RJ, Wilkes MM (2003) Hypoalbumin- we learned in recent years? Curr Opin Clin Nutr Metab Care 18: 415-421. emia in acute illness: Is there a rationale for intervention? A meta-analysis of cohort studies and controlled trials. Ann Surg 237: 319-334. 46. Tormey WP, O’Brien PA (1993) Clinical associations of an increased transthyretin band in routine serum and urine protein electrophoresis. Ann Clin Biochem 30: 550-554.

Volume 5 • S1001 J Food Sci Nutr ISSN: 2470-1076, Open Access Journal DOI: 10.24966/FSN-1076/S1001

Journal of Anesthesia & Clinical Care Journal of Genetics & Genomic Sciences Journal of Addiction & Addictive Disorders Journal of , Blood Transfusion & Disorders Advances in Microbiology Research Journal of Human Advances in Industrial Biotechnology Journal of Hospice & Palliative Medical Care Journal of Agronomy & Agricultural Science Journal of Internal Medicine & Primary Healthcare Journal of AIDS Clinical Research & STDs Journal of Infectious & Non Infectious Diseases Journal of Alcoholism, Drug Abuse & Substance Dependence Journal of Light & Laser: Current Trends Journal of Disorders & Journal of Modern Chemical Sciences Journal of Alternative, Complementary & Integrative Medicine Journal of Medicine: Study & Research Journal of Alzheimer’s & Neurodegenerative Diseases Journal of Nanotechnology: & Nanobiotechnology Journal of & Journal of & Clinical Journal of Animal Research & Veterinary Science Journal of & Renal Therapy Archives of Zoological Studies Journal of Non Invasive Vascular Investigation Archives of Journal of , & Journal of Atmospheric & Earth-Sciences Journal of Obesity & Weight Loss Journal of Aquaculture & Fisheries Journal of Orthopedic Research & Physiotherapy Journal of Biotech Research & Biochemistry Journal of Otolaryngology, Head & Neck Surgery Journal of Brain & Neuroscience Research Journal of Protein Research & Bioinformatics Journal of Cancer Biology & Treatment Journal of Clinical & Medical Research Journal of : Study & Research Journal of Pharmacology, Pharmaceutics & Pharmacovigilance Journal of Cell Biology & Cell Metabolism Journal of Physical Medicine, Rehabilitation & Disabilities Journal of Clinical & Therapy Journal of Plant Science: Current Research Journal of Clinical & Immunotherapy Journal of , & Journal of Clinical Studies & Medical Case Reports Journal of Pulmonary Medicine & Respiratory Research Journal of Community Medicine & Care Journal of Practical & Professional Nursing Current Trends: Medical & Biological Engineering Journal of , & Journal of Cytology & Tissue Biology Journal of Stem Cells Research, Development & Therapy Journal of : Oral Health & Cosmesis Journal of Surgery: Current Trends & Innovations Journal of Diabetes & Metabolic Disorders Journal of Toxicology: Current Research Journal of Dairy Research & Technology Journal of Translational Science and Research Journal of Trauma & Surgical Care Trends in Anatomy & Physiology Journal of Environmental Science: Current Research Journal of Vaccines Research & Vaccination Journal of Food Science & Nutrition Journal of Virology & Antivirals Journal of Forensic, Legal & Investigative Sciences Archives of Surgery and Surgical Education

Journal of Gastroenterology & Research and Injury Care Journal Journal of Gerontology & Geriatric Medicine International Journal of Case Reports and Therapeutic Studies

Submit Your Manuscript: http://www.heraldopenaccess.us/Online-Submission.php

Herald Scholarly Open Access, 2561 Cornelia Rd, #205, Herndon, VA 20171, USA. Tel: +1-646-661-6626; E-mail: [email protected] http://www.heraldopenaccess.us/